Health

COVID-19 vaccine: Oxford-AstraZeneca up to 90% effective in late stage trial

Adenovirus vaccine can be stored at 2-8°C; company to apply for emergency authorisation

 
By Banjot Kaur
Published: Monday 23 November 2020
Oxford-AstraZeneca COVID-19 vaccine candidate’s interim results show 62-90% efficacy. Photo: Needpix.com

The novel coronavirus disease (COVID-19) vaccine candidate of Oxford University and AstraZeneca PLC inspired hope November 23, 2020, with its latest interim analysis of its Phase 3 trials. The two different dosing regimens of the same candidate have shown efficacy of 90 per cent and 62 per cent. 

The dosing regimen constituting a half dose of the vaccine, followed by a full dose, given a month apart, showed an efficacy of 90 per cent, the company said.

Another regimen, constituting of two full doses given one month apart showed an efficacy of 62 per cent.

Thus, the average efficacy was shown to be 70 per cent

The interim results announced by Pfizer Inc and Moderna Inc earlier this month for their respective candidates were 90 per cent and 94.5 per cent respectively. 

A higher dose would mean better efficacy in popular perception. However, the Oxford-AstraZeneca candidate shows otherwise.

“The immune system has its own way of functioning and not how we would like to think. These results essentially show if you run over the top, you are not going to see much of a result,” Gangadeep Kang, a renowned virologist told Down To Earth

“When you give a certain dose, you see the response up to a certain level and realise that beyond that level, the response saturates,” she added.

Usually, different regimens of the same candidate are tested in Phase 2 where you play with dosing and scheduling and then wait for results.

“But here, you had to compress the timeline. Therefore, you quickly proceeded to Phase 3, where an interim analysis showed that, yes, you have a positive result and now you can do standardisation for dosing and scheduling,” Kang said. 

However, shouldn’t lower dosing producing better results also be true for other COVID-19 vaccine candidates too that have shown good results in their interim analysis?

Kang said one had to keep in mind that both the other candidates of Pfizer and Moderna were messenger Ribonucleic Acid (mRNA) vaccines while Oxford-AstraZeneca was an adenovirus vaccine. In other words, the platforms by which these vaccines delivered the antigen (which triggered the immune response) in the body were different.

“mRNA is a chemical compound that is constructed artificially. In the other case, you have grown an engineered adenovirus,” Kang said. Therefore, the above argument might not be same and true for different candidates, she added. 

mRNA has been sequenced from the novel coronavirus SARS-CoV-2 in the laboratory. When mRNA goes inside the body, it tells the cells to produce copies of spike proteins (Spike proteins are present on the surface of the coronavirus, protruding out of it).

This, in turn, stimulates the immune system to produce antibodies against the spike protein. So when an actual novel coronavirus infects the body, the antibodies would be present to trigger an immune response. Thus, the antigen, in this case, is nothing but the protein.

Adenovirus, on the other hand, is the common cold virus affecting chimpanzees. They are genetically modified artificially so that it can’t go on producing its replicas as it goes inside body. Once injected, it releases the spike protein. As the virus goes on infecting cells, more and more spike proteins are created against which an immune response is generated.

Vaccine prospects

The fact that a lower dose regimen worked better than a higher dose was also a logistical advantage. 

“The report that an initial half dose then a full dose is even better than two full doses is great news, potentially increasing the number of people that can be vaccinated and reducing costs,” Peter Openshaw, professor of experimental medicine at Imperial College London, said in a reaction to November 23’s development. 

Another significant difference was that the temperature required to store the Oxford vaccine was higher than Pfizer’s and Moderna’s. Oxford’s vaccine has to be stored at 2-8 degrees Celsius while Pfizer’s and Moderna’s  vaccines has to be stored at minus 70°C and minus 20°C, respectively. The ultra-cold chains requirement for distribution across countries is a big challenge for policymakers. 

AstraZeneca will submit the interim to drug regulators in the UK, Europe and Brazil for getting an emergency use authorisation (EUA). A restricted EUA is granted by a regulator of a country on the basis of interim results without waiting for the results of the full Phase 3. 

November 23’s Oxford vaccine’s interim results were based on the ongoing Phase 3 trials on 23,000 participants in the UK, South Africa and Brazil. Further trials are also going on in India, being carried on by the Pune-based Serum Institute. The Institute is also producing the vaccine at scale. Other than India, the trials are also going on in the United States, Kenya and Japan. 

“AstraZeneca already has international agreements in place to supply three billion doses of the vaccine, with access being built through more than 30 supply agreements and partner networks,” an Oxford University press release said. 

Of all the three vaccine candidates, which one could be a better bet for India?

“I would put my bet on the Oxford vaccine for logistical reasons, including its price. It is cheaper than the other two. Also, unlike the other two candidates that use the mRNA platform which is new, the adenovirus virus platform has been used in several other vaccines. So, if I were a public health policymaker for India, depending on further results, I would go for something that is already tried and tested,” Kang said. 

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